Food socialization of children with Prader-Willi syndrome: an interdisciplinary problematization.

Eating "disorders" of people with Prader-Willi syndrome are frequently reported in the biomedical literature. The eating behaviors are presented as a syndrome-specific trajectory over the course of a lifetime. Infants initially show anorexic behavior, which then develops into hyperphagia that lasts from childhood to adulthood and is characterized by strong cravings for food and relentless thinking about it. However, the sociocultural determinants of these food practices are not fully understood. In the first section of this article, we carry out a literature review of medical articles published on disordered eating in children with PWS. The second section draws on a social science perspective and offers an interdisciplinary problematization using the concept of food socialization. To conclude, the third section explores the challenges facing research and new questions that emerge from the alternative problematization that is the PWS Food Social Norms Internalization (FSNI) theory.

Amygdala hyperactivation relates to eating behaviour: a potential indicator of food addiction in Prader-Willi syndrome.

Prader-Willi syndrome is a rare neurodevelopmental genetic disorder characterized by various endocrine, cognitive and behavioural problems. The symptoms include an obsession for food and reduced satiety, which leads to hyperphagia and morbid obesity. Neuropsychological studies have reported that Prader-Willi patients display altered social interactions with a specific weakness in interpreting social information and responding to them, a symptom close to that observed in autism spectrum disorders. In the present case-control study, we hypothesized that brain regions associated with compulsive eating behaviour would be abnormally activated by food-related odours in Prader-Willi syndrome, as these can stimulate the appetite and induce hunger-related behaviour. We conducted a brain imaging study using the olfactory modality because odours have a high-hedonic valence and can cause stronger emotional reactions than other modalities. Further, the olfactory system is also intimately associated with the endocrine regulation of energy balance and is the most appropriate modality for studies of Prader-Willi syndrome. A total of 16 Prader-Willi participants were recruited for this study, which is a significant achievement given the low incidence rate of this rare disease. The second group of 11 control age-matched subjects also participated in the brain imaging study. In the MRI scanner, using an MRI-compatible olfactometer during 56 block sessions, we randomly presented two odours (tulip and caramel), which have different hedonic valence and a different capacity to arouse hunger-related behaviour. Our results demonstrate that Prader-Willi participants have abnormal activity in the brain reward system that regulates eating behaviour. Indeed, we found that these patients had right amygdala activity up to five times higher in response to a food odour (caramel) compared with the tulip odour. In contrast, age-matched control participants had similar activity levels in response to both odours. The amygdala activity levels were found to be associated with the severity of the hyperphagia in Prader-Willi patients. Our results provide evidence for functional alteration of the right amygdala in Prader-Willi syndrome, which is part of the brain network involved in food addiction modulated by the ghrelin and oxytocin systems, which may drive the hyperphagia. Our study provides important new insights into the functioning of emotion-related brain circuits and pathology, and it is one of the few to explore the dysfunction of the neural circuits involved in emotion and addiction in Prader-Willi syndrome. It suggests new directions for the exploration and remediation of addictive behaviours.

Impact of Deprivation on Obesity in Children with PWS.

Our study aimed to evaluate the social deprivation score in families with a child with Prader-Willi syndrome (PWS) and analyze its impact on the occurrence of obesity in the affected child. We included 147 children with PWS followed in our reference center with Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres by the EPICES score. Deprivation (EPICES ≥ 30) was found in 25.9% of the population. Compared with the non-obese children, children with obesity had more deprived families, 50.0 vs. 18.0% (p = 0.0001); were older, with a median of 10.1 vs. 6.0 years (p = 0.0006); were less frequently treated with growth hormone (GH), 80.6 vs. 91.9% (p = 0.07). The mothers of obese children were more frequently obese, 46.9 vs. 13.3% (p < 0.0001), and achieved high study levels less frequently (≥Bac+2), 40.9 vs. 70.1% (p = 0.012). The multivariate logistic regression indicated that age, living in a deprived family, and having a mother with overweight/obesity were significantly associated with an increased risk of obesity (respectively, OR = 3.31 (1.26−8.73) and OR = 6.76 (2.36−19.37)). The same risk factors of obesity observed in the general population were found in children with PWS. Families at risk, including social deprivation, will require early identification and a reinforced approach to prevent obesity.

Is ghrelin a biomarker of early-onset scoliosis in children with Prader-Willi syndrome?

BACKGROUND: Adolescents with idiopathic scoliosis display high ghrelin levels. As hyperghrelinemia is found in patients with PWS and early-onset scoliosis (EOS) is highly prevalent in these patients, our aims were to explore (1) whether ghrelin levels differ between those with and without EOS and correlate with scoliosis severity, and (2) whether ghrelin levels in the first year of life are associated with the later development of EOS. METHODS: We used a case control study design for the first question and a longitudinal design for the second. Patients with PWS having plasma ghrelin measurements recorded between 2013 and 2018 in our database were selected and 30 children < 10 years old with EOS and 30 age- and BMI-matched controls without EOS were included. The Cobb angle at diagnosis was recorded. In addition, 37 infants with a ghrelin measurement in the first year of life were followed until 4 years of age and assessed for EOS. Total ghrelin (TG), acylated (AG) and unacylated ghrelin (UAG), and the AG/UAG ratio were analyzed. RESULTS: EOS children had an AG/UAG ratio statistically significantly lower than controls. The Cobb angle was positively correlated with TG and UAG. TG and AG in the first year of life were higher in infants who later develop EOS without reaching a statistically significant difference. CONCLUSIONS: Our results suggest that ghrelin may play a role in the pathophysiology of EOS in PWS. Higher ghrelinemia in the first year of life required careful follow-up for EOS.

Bank of Digital Filters for Identification of Combined Drug Products in a French Public Database.

Drugs information systems, prescription support softwares, and drug decision support systems need to reason on drug properties. Combined pharmaceutical products need to be considered specifically because they may require a specific processing. Hence, they also need to be identified to automate the population of databases with up-to-date property values. We defined a set of digital filters designed for the identification of antibiotics in a public database. Four different filters are proposed, to be combined to extract the relevant information. Evaluation was conducted to combine filters and retrieve information about rand combined antibiotics with success. However, information provided in the structured files of the French drug database is limited; information provided in the HTML files suffers from a lack of quality. Hence, reuse of this data and this information should be performed very cautiously.

A study of voice and non-voice processing in Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. It manifests itself in endocrine and cognitive problems, including highly pronounced hyperphagia and severe obesity. In many cases, impaired acquisition of social and communication skills leads to autism spectrum features, and individuals with this syndrome are occasionally diagnosed with autism spectrum disorder (ASD) using specific scales. Given that communicational skills are largely based on vocal communication, it is important to study human voice processing in PWS. We were able to examine a large number of participants with PWS (N = 61) recruited from France's national reference center for PWS and other hospitals. We tested their voice and nonvoice recognition abilities, as well as their ability to distinguish between voices and nonvoices in a free choice task. We applied the hierarchical drift diffusion model (HDDM) with Bayesian estimation to compare decision-making in participants with PWS and controls. RESULTS: We found that PWS participants were impaired on both voice and nonvoice processing, but displayed a compensatory ability to perceive voices. Participants with uniparental disomy had poorer voice and nonvoice perception than participants with a deletion on chromosome 15. The HDDM allowed us to demonstrate that participants with PWS need to accumulate more information in order to make a decision, are slower at decision-making, and are predisposed to voice perception, albeit to a lesser extent than controls. CONCLUSIONS: The categorization of voices and nonvoices is generally preserved in participants with PWS, though this may not be the case for the lowest IQ.

Face processing and exploration of social signals in Prader-Willi syndrome: a genetic signature.

BACKGROUND: Faces are critical social cues that must be perfectly processed in order to engage appropriately in everyday social interactions. In Prader-Willi Syndrome (PWS), a rare genetic disorder characterized by cognitive and behavioural difficulties including autism spectrum disorder, the literature referring to face processing is sparse. Given reports of poor social interactions in individuals with PWS, we sought to assess their face and emotion recognition skills during eyetracking recordings. RESULTS: Compared with controls, patients with PWS performed more poorly on face/emotion recognition. We observed atypical facial exploration by patients with maternal disomy. These patients looked preferentially at the mouth region, whereas patients with a deletion and controls were more attracted to the eye region. During social scenes, the exploration became more atypical as the social content increased. CONCLUSIONS: Our comprehensive study brings new insights into the face processing of patients with PWS. Atypical facial exploration was only displayed by patients with the maternal disomy subtype, corresponding to their higher rate of autism spectrum disorder. This finding strongly argues in favor of early identification of this genetic subgroup in order to optimize care by implementing tailored interventions for each patient as soon as possible.

Causes of death in Prader-Willi syndrome: lessons from 11 years' experience of a national reference center.

BACKGROUND: In the last 20 years, substantial improvements have been made in the diagnosis, treatment and management of patients with Prader-Willi syndrome (PWS). Few data on causes of death are available since those improvements were made. Our study assessed the causes of death among French patients with PWS over the first 11 years of experience of the nationwide French Reference Center for PWS (FRC-PWS). METHODS: Our study relied on two sources of mortality information at national level between 2004 and 2014: The French Epidemiological Centre for the Medical Causes of Death (CépiDc) Registry and the FRC-PWS database. Causes of death were classified into seven categories: respiratory, cardiovascular, gastrointestinal, severe infection, sudden death, other causes, and unknown. Descriptive statistics were calculated separately for children (< 18 years-old) and adults (≥18 years-old). RESULTS: One hundred and four deaths were identified in France from 2004 to 2014. The median age at death was 30 years, ranging from less than 1 month to 58 years. Seventeen deaths occurred in patients under 18 years, with 70% of them in children under 2 years. Respiratory causes accounted for more than 50% of the deaths in patients with PWS in both children and adults. Both cause and age of death did not significantly differ according to gender or genetic subtype. CONCLUSIONS: Patients with PWS die prematurely due to a respiratory cause in most cases at all ages. In those adult patients with data on obesity, 98% were reported to be obese.

Prader-Willi syndrome: A model for understanding the ghrelin system.

Subsequent to the discovery of ghrelin as the endogenous ligand of growth hormone secretagogue receptor 1a, this unique gut peptide has been found to exert numerous physiological effects, such as appetite stimulation and lipid accumulation via the central regulating mechanisms in the hypothalamus, stimulation of gastric motility, regulation of glucose metabolism and brown fat thermogenesis, and modulation of stress, anxiety, taste sensation, reward-seeking behaviour and the sleep/wake cycle. Prader-Willi syndrome (PWS) has been described as a unique pathological state characterised by severe obesity and high circulating levels of ghrelin. It was hypothesised that hyperghrelinaemia would explain at least a part of the feeding behaviour and body composition of PWS patients, who are characterised by hyperphagia, an obsession with food and food-seeking, and increased adiposity. Initially, the link between hyperghrelinaemia and growth hormone deficiency, which is observed in 90% of the children with PWS, was not fully understood. Over the years, however, the increasing knowledge on ghrelin, PWS features and the natural history of the disease has led to a more comprehensive description of the abnormal ghrelin system and its role in the pathophysiology of this rare and complex neurodevelopmental genetic disease. In the present study, we (a) present the current view of PWS; (b) explain its natural history, including recent data on the ghrelin system in PWS patients; and (c) discuss the therapeutic approach of modulating the ghrelin system in these patients and the first promising results.

The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome.

BACKGROUND AND OBJECTIVES: Patients with Prader-Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother-infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.

Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom.

BACKGROUND: Infant-mother interaction is a set of bidirectional processes, where the baby is not only affected by the influences of his caregiver, but is also at the origin of considerable modifications. The recent discovery of biological correlates of synchrony during interaction validated its crucial value during child development. Here, we focus on the paradigmatic case of Prader-Willi Syndrome (PWS) where early endocrinal dysfunction is associated with severe hypotonia and early feeding disorder. As a consequence, parent-infant interaction is impaired. In a recent study (Tauber et al., 2017), OXT intranasal infusion was able to partially reverse the feeding phenotype, infant's behavior and brain connectivity. This article details the interaction profile found during feeding in these dyads and their improvement after OXT treatment. METHODS: Eighteen infants (≤6months) with PWS were recruited and hospitalized 9days in a French reference center for PWS where they were treated with a short course of intranasal OXT. Social withdrawal behavior and mother-infant interaction were assessed on videos of feeding before and after treatment using the Alarm Distress Baby (ADBB) Scale and the Coding Interactive Behavior (CIB) Scale. Raters were blind to treatment status. RESULTS: At baseline, infants with PWS showed hypotonia, low expressiveness of affects, fatigability and poor involvement in the relationship with severe withdrawal. Parents tended to adapt to their child difficulties, but the interaction was perturbed, tense, restricted and frequently intrusive with a forcing component during the feeding situation. After OXT treatment, infants were more alert, less fatigable, more expressive, and had less social withdrawal. They initiated mutual activities and were more engaged in relationships through gaze, behavior, and vocalizations. They had a better global tonicity with better handling. These modifications helped the parents to be more sensitive and the synchrony of the dyad was in a positive transactional spiral. CONCLUSION: Dys-synchrony can be induced by children's pathology as well as parental pathology with emotional and developmental impact in the both cases. The PWS paradigm shows us the necessity to sustain early parents-child relationship to avoid establishment of a negative transactional pattern of interaction that can impact child's development.

Casein Compared with Whey Proteins Affects the Organization of Dietary Fat during Digestion and Attenuates the Postprandial Triglyceride Response to a Mixed High-Fat Meal in Healthy, Overweight Men.

BACKGROUND: Postprandial lipemia is a risk factor for cardiovascular disease. The potential impacts of the type/nature of dietary protein on postprandial lipemia and associated dysregulations have been insufficiently investigated. OBJECTIVE: We investigated the postprandial effect of including in a high-fat meal some milk protein fractions that markedly differ in their physicochemical properties and composition [either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC)]. METHODS: The protein fractions were incorporated as 15% energy in a high-fat meal in a 3-period, crossover postprandial study of 10 healthy overweight men with an elevated waist circumference (>94 cm). We measured postprandial changes in plasma lipids, amino acids, glucose, and oxidative stress markers, vascular function (using pulse contour analysis), and low-grade inflammation (using plasma markers). We also characterized in vitro the meal structures, including the size of the fat globule, and possible changes during digestion. RESULTS: The type of protein did not affect postprandial plasma glucose, amino acids, insulin, or nonesterified fatty acids, but, compared with WHE and LAC, which did not differ, CAS markedly reduced postprandial triglycerides (TGs), achieving a 22 ± 10% reduction in the 6-h area under the curve (P < 0.05). Similar trends were shown for plasma chylomicrons [apolipoprotein (apo)B-48; P < 0.05]. However, there were no significant differences between the meals regarding postprandial oxidative stress (plasma hydroperoxides and malondialdehyde), endothelial dysfunction (salbutamol-induced changes in pulse contour analysis), or low-grade inflammation. In vitro studies showed that when the pH of the meal decreased to stomach pH values, the reduction in the solubility of casein resulted in a phase separation between fat and protein, whereas the proteins in the other meals remained suspended with fat globules. CONCLUSION: In healthy overweight men, casein has specific physical interactions with fat that affect postprandial TGs, leading to the formation of fewer chylomicrons or an increase in chylomicron clearance. This trial was registered at clinicaltrials.gov as NCT00931151.

Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery.

Bariatric surgery is the most effective long term weight-loss therapy for severe and morbidly obese patients. Melanocortin-4 Receptor (MC4R) mutations, the most frequent known cause of monogenic obesity, affect the regulation of energy homeostasis. The impact of such mutations on weight loss after bariatric surgery is still debated.The objective is to determine the impact of MC4R status on weight loss in obese subjects over one year after bariatric surgery.A total of 648 patients, who were referred to bariatric surgery in a single clinical nutrition department, were genotyped for their MC4R status. The following four groups were categorized: functional MC4R mutations, MC4R single nucleotide polymorphisms (SNPs): Val103Ile (V103L) and Ile251Leu (I251L), MC4R variant rs17782313 (downstream of MC4R) and MC4R SNP A-178C on the promoter. Each patient was matched with two randomly paired controls without mutation. Matching factors were age, sex, baseline weight and type of surgery procedure (Roux-en-Y gastric bypass and adjustable gastric banding). We compared weight loss between cases and controls at 3, 6 and 12 months after surgery.Among 648 patients, we identified 9 carriers of functional MC4R mutations, 10 carriers of MC4R V103L and I251L SNPs, 7 carriers of the rs17792313 variant and 22 carriers of the A-178C SNP. Weight loss at 3, 6 and 12 months did not differ between cases and controls, whatever the MC4R mutations.This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery.